Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis
Authors: Joy W. Chang, Kara Kliewer, Emily Haller, Amanda Lynett, Bethany Doerfler, David A. Katzka, Kathryn A. Peterson, Evan S. Dellon, Nirmala Gonsalves, Seema S. Aceves, Pablo Abonia, Dan Atkins, Peter A. Bonis, Mirna Chehade, Gary W. Falk, Glenn T. Furuta, Sandeep K. Gupta, Amir F. Kagalwalla, Ellyn Kodroff, Scholeigh Kyle, John Leung, Paul Menard-Katcher, Sabina Mir, Vincent A. Mukkada, Robert Pesek, Marc E. Rothenberg, Jonathan M. Spergel, Mary Jo Strobel, Joshua B. Wechsler
Journal: Clinical Gastroenterology and Hepatology (2023)

Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers. Dietary therapy for short- and long-term management of eosinophilic esophagitis is an effective yet poorly understood and underutilized treatment strategy. Despite several prospective trials demonstrating the efficacy of dietary therapies, successful clinical implementation is hampered by the need for a multidisciplinary approach including dietitian support and provider expertise. The availability of these resources is not readily available to most gastroenterologists. Without standardized guidance on starting or completing the diet for gastrointestinal providers and/or consulting dietitians, provider attitudes toward dietary therapy vary greatly depending on familiarity and knowledge gaps in using diet therapy. This review aims to summarize evidence in support of dietary therapy in eosinophilic esophagitis while providing guidance on initiation and implementation of dietary therapy for providers. Eosinophilic esophagitis (EoE) is a chronic inflammatory immune-mediated disease affecting both children and adults, characterized by symptoms of esophageal dysfunction, eosinophilia, and fibrosis of the esophagus. A diagnosis of EoE is made based on symptoms such as dysphagia, food bolus obstruction, and less commonly heartburn, globus, or poor feeding; endoscopic mucosal findings of longitudinal furrows, rings, and strictures; and the presence of esophageal eosinophilia (>15 eosinophils per high-power field [eos/hpf]).1Furuta G.T. Liacouras C.A. Collins M.H. et al.Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.Gastroenterology. 2007; 133: 1342-1363Abstract Full Text Full Text PDF PubMed Scopus (1407) Google Scholar, 2Dellon E.S. Gonsalves N. Hirano I. et al.ACG clinical guideline: evidence based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).Am J Gastroenterol. 2013; 108: 679-692Crossref PubMed Scopus (846) Google Scholar, 3Lucendo A.J. Molina-Infante J. Arias A. et al.Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults.United European Gastroenterol J. 2017; 5: 335-358Crossref PubMed Scopus (619) Google Scholar This eosinophil-predominant inflammation characteristic of EoE is driven and precipitated by food antigens as affirmed by effective treatment of the disease with diet elimination of specific food allergens.4Markowitz J.E. Spergel J.M. Ruchelli E. et al.Elemental diet is an effective treatment for eosinophilic esophagitis in children and adolescents.Am J Gastroenterol. 2003; 98: 777-782Crossref PubMed Scopus (512) Google Scholar, 5Kagalwalla A.F. Sentongo T.A. Ritz S. et al.Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2006; 4: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (601) Google Scholar, 6Spergel J.M. Brown-Whitehorn T.F. Cianferoni A. et al.Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet.J Allergy Clin Immunol. 2012; 130: 461-467Abstract Full Text Full Text PDF PubMed Scopus (305) Google Scholar, 7Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (504) Google Scholar, 8Peterson K.A. Byrne K.R. Vinson L.A. et al.Elemental diet induces histologic response in adult eosinophilic esophagitis.Am J Gastroenterol. 2013; 108: 759-766Crossref PubMed Scopus (195) Google Scholar, 9Lucendo A.J. Arias A. Gonzalez-Cervera J. et al.Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.J Allergy Clin Immunol. 2013; 131: 797-804Abstract Full Text Full Text PDF PubMed Scopus (321) Google Scholar, 10Gonsalves N. Doerfler B. Schwartz S. et al.Prospective trial of four food elimination diet demonstrates comparable effectiveness in the treatment of adult and pediatric eosinophilic esophagitis.Gastroenterology. 2013; 144S-154Abstract Full Text PDF Google Scholar, 11Arias A. Gonzalez-Cervera J. Tenias J.M. et al.Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis.Gastroenterology. 2014; 146: 1639-1648Abstract Full Text Full Text PDF PubMed Scopus (386) Google Scholar, 12Molina-Infante J. Arias A. Barrio J. et al.Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study.J Allergy Clin Immunol. 2014; 134: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar, 13Warners M.J. Vlieg-Boerstra B.J. Verheij J. et al.Elemental diet decreases inflammation and improves symptoms in adult eosinophilic oesophagitis patients.Aliment Pharmacol Ther. 2017; 45: 777-787Crossref PubMed Scopus (66) Google Scholar, 14Kagalwalla A.F. Wechsler J.B. Amsden K. et al.Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2017; 15: 1698-1707Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 15Wechsler J.B. Schwartz S. Ross J.N. et al.Cow's milk elimination for treatment of eosinophilic esophagitis: a prospective pediatric study.Gastroenterology. 2017; 152S-855Abstract Full Text PDF Google Scholar, 16Mayerhofer C. Kavallar A.M. Aldrian D. et al.Efficacy of elimination diets in eosinophilic esophagitis: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2023; (Jan 31 [E-pub ahead of print])Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Current first-line effective treatments aimed at targeting inflammation and preventing fibrostenotic complications such as esophageal strictures and food impactions include food elimination diets and medications such as proton pump inhibitors, topical corticosteroids (TCSs), and the recently approved anti-interleukin-4 receptor biologic, dupilumab.17Dellon E.S. Rothenberg M.E. Collins M.H. et al.Dupilumab in adults and adolescents with eosinophilic esophagitis.N Engl J Med. 2022; 387: 2317-2330Crossref PubMed Scopus (35) Google Scholar, 18Hirano I. Chan E.S. Rank M.A. et al.AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis.Gastroenterology. 2020; 158: 1776-1786Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar, 19Hirano I. Dellon E.S. Hamilton J.D. et al.Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis.Gastroenterology. 2020; 158: 111-122.e10Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar Medications offer short response time and relative ease of use, but out-of-pocket payments can incur high costs for patients and require inconvenient and nonstandard preparations. Elimination diets offer a nonpharmacologic alternative to disease control, and studies to date demonstrate efficacy similar to that of medications, but require adherence to a strict diet and frequent endoscopies to identify food triggers. Studies to date show that both diet and medications are effective in inducing and maintaining long-term disease remission, reducing the risk of food impactions, and improving health-related quality of life.20Cotton C.C. Eluri S. Wolf W.A. et al.Six-food elimination diet and topical steroids are effective for eosinophilic esophagitis: a meta-regression.Dig Dis Sci. 2017; 62: 2408-2420Crossref PubMed Scopus (59) Google Scholar, 21Dellon E.S. Woosley J.T. Arrington A. et al.Efficacy of budesonide vs fluticasone for initial treatment of eosinophilic esophagitis in a randomized controlled trial.Gastroenterology. 2019; 157: 65-73Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 22Kuchen T. Straumann A. Safroneeva E. et al.Swallowed topical corticosteroids reduce the risk for long-lasting bolus impactions in eosinophilic esophagitis.Allergy. 2014; 69: 1248-1254Crossref PubMed Scopus (98) Google Scholar, 23Reed C.C. Fan C. Koutlas N.T. et al.Food elimination diets are effective for long-term treatment of adults with eosinophilic oesophagitis.Aliment Pharmacol Ther. 2017; 46: 836-844Crossref PubMed Scopus (65) Google Scholar, 24Safroneeva E. Coslovsky M. Kuehni C.E. et al.Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.Aliment Pharmacol Ther. 2015; 42: 1000-1010Crossref PubMed Scopus (67) Google Scholar As such, both are recommended as first-line treatments for EoE.2Dellon E.S. Gonsalves N. Hirano I. et al.ACG clinical guideline: evidence based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE).Am J Gastroenterol. 2013; 108: 679-692Crossref PubMed Scopus (846) Google Scholar To date, there are no comparative efficacy studies between diet and pharmacologic treatments.25ClinicalTrials.gov. Search results: eosinophilic esophagitis.https://clinicaltrials.gov/ct2/results?cond=eosinophilic+esophagitis&term=&cntry=&state=&city=&dist=Date accessed: May 13, 2021Google Scholar Diet therapy can be burdensome for patients to navigate and challenging for clinicians to implement. Consequences of poorly executed diet therapies include overly restrictive food elimination, compromised nutrition or micronutrient deficiency, lack of patient compliance or inadvertent exposures to food antigens, excess costs, "wasted" endoscopic evaluations, misinterpreting refractory disease from nonadherence, and ultimately persistent disease.26Wolf W.A. Huang K.Z. Durban R. et al.The six-food elimination diet for eosinophilic esophagitis increases grocery shopping cost and complexity.Dysphagia. 2016; 31: 765-770Crossref PubMed Scopus (40) Google Scholar Success with diet therapy can be augmented by partnering with a dietitian, but access to this clinical resource is not universal and diet education often falls to the clinician.27Chang J.W. Kliewer K. Katzka D.A. et al.Provider beliefs, practices, and perceived barriers to dietary elimination therapy in eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 2071-2074Crossref PubMed Scopus (5) Google Scholar,28Groetch M. Venter C. Skypala I. et al.Dietary therapy and nutrition management of eosinophilic esophagitis: a work group report of the American Academy of Allergy, Asthma, and Immunology.J Allergy Clin Immunol Pract. 2017; 5: 312-324.e29Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar To date, no standardized dietary resources for EoE exist. Our aim is to equip providers caring for EoE patients with evidence-based and practical knowledge to support patients in starting and sustaining an elimination diet for EoE. The role of food allergens in the pathogenesis of EoE was first demonstrated in a landmark study of children with EoE demonstrating clinical and histologic remission on a hypoallergenic amino acid–based elemental formula.29Kelly K.J. Lazenby A.J. Rowe P.C. et al.Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.Gastroenterology. 1995; 109: 1503-1512Abstract Full Text PDF PubMed Scopus (907) Google Scholar Since then, several prospective studies have shown a high rate of disease remission on elemental formula among children and adults. Challenges, however, include poor palatability, high financial cost, lack of insurance coverage, and arduous food reintroduction requiring several endoscopies, limiting the uptake of this strategy. In contrast to this highly restrictive approach, empiric elimination diets aimed at removing the most common food triggers are now the favored dietary strategy. Major challenges to the implementation of diet therapy include the need to avoid common foods such as animal milk or wheat and the lack of accurate noninvasive testing to identify inciting food antigens. Although diets guided by allergy testing (eg, skin prick, atopy patch, serum specific IgE), were once considered as a potentially practical approach to identifying EoE food triggers, findings from studies of children and adults with EoE show poor concordance between allergy testing and true trigger foods, thus suggesting that conventional allergy testing is unreliable to identify EoE food triggers.30Assa'ad A.H. Putnam P.E. Collins M.H. et al.Pediatric patients with eosinophilic esophagitis: an 8-year follow-up.J Allergy Clin Immunol. 2007; 119: 731-738Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar, 31Rizo Pascual J.M. De La Hoz Caballer B. Redondo Verge C. et al.Allergy assessment in children with eosinophilic esophagitis.J Investig Allergol Clin Immunol. 2011; 21: 59-65PubMed Google Scholar, 32Philpott H. Nandurkar S. Royce S.G. et al.Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities.Aliment Pharmacol Ther. 2016; 44: 223-233Crossref PubMed Scopus (79) Google Scholar, 33Eckmann J.D. Ravi K. Katzka D.A. et al.Efficacy of atopy patch testing in directed dietary therapy of eosinophilic esophagitis: a pilot study.Dig Dis Sci. 2018; 63: 694-702Crossref PubMed Scopus (32) Google Scholar Furthermore, suspected triggers of inflammation identified through these methods may be detrimental if patients are prescribed overly restrictive diets based on testing. While novel tests are under development to identify food triggers, these are still considered experimental and not available for use in routine practice.34Pyne A.L. Hazel M.W. Uchida A.M. et al.Oesophageal secretions reveal local food-specific antibody responses in eosinophilic oesophagitis.Aliment Pharmacol Ther. 2022; 56: 1328-1336Crossref PubMed Scopus (3) Google Scholar, 35Warners M.J. Terreehorst I. van den Wijngaard R.M. et al.Abnormal responses to local esophageal food allergen injections in adult patients with eosinophilic esophagitis.Gastroenterology. 2018; 154: 57-60.e2Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 36Dellon E.S. Guo R. McGee S.J. et al.A novel allergen-specific immune signature-directed approach to dietary elimination in eosinophilic esophagitis.Clin Transl Gastroenterol. 2019; 10e00099Crossref PubMed Scopus (20) Google Scholar Despite the perceived challenges of dietary therapy for EoE, this approach is increasing in popularity due to patient preference for natural approaches, the use of less restrictive diets, and avoidance of pharmacologic therapies. Patients with EoE report high acceptance of diets and would recommend the diet to others.37Wang R. Hirano I. Doerfler B. et al.Assessing adherence and barriers to long-term elimination diet therapy in adults with eosinophilic esophagitis.Dig Dis Sci. 2018; 63: 1756-1762Crossref PubMed Scopus (58) Google Scholar They also value shared decision making around treatment choices for EoE and struggle with providers who lacked disease-related knowledge or did not support diet treatment as an acceptable therapeutic choice.38Chang J.W. Chen V.L. Rubenstein J.H. et al.What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities.Dis Esophagus. 2022; 35: doab073Crossref PubMed Scopus (2) Google Scholar,39Chang J.W. Rubenstein J.H. Mellinger J.L. et al.Motivations, barriers, and outcomes of patient-reported shared decision making in eosinophilic esophagitis.Dig Dis Sci. 2021; 66: 1808-1817Crossref PubMed Scopus (12) Google Scholar Conversely, prior studies show that physicians prefer to use medications over diet for EoE, view diet as less effective, lack access to dietitian support, and falsely perceive that patients are not interested in or unable to adhere to food elimination.27Chang J.W. Kliewer K. Katzka D.A. et al.Provider beliefs, practices, and perceived barriers to dietary elimination therapy in eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 2071-2074Crossref PubMed Scopus (5) Google Scholar,40Eluri S. Iglesia E.G.A. Massaro M. et al.Practice patterns and adherence to clinical guidelines for diagnosis and management of eosinophilic esophagitis among gastroenterologists.Dis Esophagus. 2020; 33doaa025Crossref Scopus (13) Google Scholar, 41King J. Khan S. Eosinophilic esophagitis: perspectives of adult and pediatric gastroenterologists.Dig Dis Sci. 2010; 55: 973-982Crossref PubMed Scopus (16) Google Scholar, 42Peery A.F. Shaheen N.J. Dellon E.S. Practice patterns for the evaluation and treatment of eosinophilic oesophagitis.Aliment Pharmacol Ther. 2010; 32: 1373-1382Crossref PubMed Scopus (58) Google Scholar, 43Chang J.W. Saini S.D. Mellinger J.L. et al.Management of eosinophilic esophagitis is often discordant with guidelines and not patient-centered: results of a survey of gastroenterologists.Dis Esophagus. 2019; 32: doy133Crossref PubMed Scopus (30) Google Scholar While pharmacologic therapies offer relative ease of use and are generally well tolerated, short-term side effects of TCSs include oropharyngeal and esophageal Candida infections, and there may also be potential and unquantified long-term adverse effects (eg, adrenal suppression) from chronic TCS and proton pump inhibitor use.44Dellon E.S. Katzka D.A. Collins M.H. et al.Safety and efficacy of budesonide oral suspension maintenance therapy in patients with eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2019; 17: 666-673.e8Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 45Freedberg D.E. Kim L.S. Yang Y.X. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association.Gastroenterology. 2017; 152: 706-715Abstract Full Text Full Text PDF PubMed Scopus (490) Google Scholar, 46Fagen A.H. Russin M. Chang J.W. Iatrogenic Cushing's syndrome in eosinophilic esophagitis: a rare complication of swallowed topical corticosteroids.American Journal of Gastroenterology. 2022; 117: e1568Crossref Google Scholar Although the safety profile of dupilumab is favorable, known side effects include injection-site reaction, ocular complications of conjunctivitis and ulcerative keratitis, joint pain, and oral herpes.17Dellon E.S. Rothenberg M.E. Collins M.H. et al.Dupilumab in adults and adolescents with eosinophilic esophagitis.N Engl J Med. 2022; 387: 2317-2330Crossref PubMed Scopus (35) Google Scholar,47Eichenfield L.F. Bieber T. Beck L.A. et al.Infections in dupilumab clinical trials in atopic dermatitis: a comprehensive pooled analysis.Am J Clin Dermatol. 2019; 20: 443-456Crossref PubMed Scopus (116) Google Scholar, 48Neagu N. Dianzani C. Avallone G. et al.Dupilumab ocular side effects in patients with atopic dermatitis: a systematic review.J Eur Acad Dermatol Venereol. 2022; 36: 820-835Crossref PubMed Scopus (14) Google Scholar, 49Simpson E.L. Bieber T. Guttman-Yassky E. et al.Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.N Engl J Med. 2016; 375: 2335-2348Crossref PubMed Scopus (1239) Google Scholar The cost of off-label topical corticosteroids can be prohibitively expensive, as a 6-week course of budesonide respules 1 mg twice daily is estimated to cost $1613–$1723, and in a recent cost utility analysis, the median cost was $2316 per quarter.50Pulmicort respules. Truven Health Analytics, Inc.www.micromedexsolutions.comDate accessed: November 3, 2020Google Scholar,51Alexander J.A. Topical steroid therapy for eosinophilic esophagitis.Gastroenterol Hepatol (N Y). 2014; 10: 327-329PubMed Google Scholar Compounded budesonide suspensions may offer more affordable options, but downsides include variations in formulation, pharmacy practice patterns, and insurance coverage.52Joshi S. Rubenstein J.H. Dellon E.S. et al.Variability in practices of compounding budesonide for eosinophilic esophagitis.Am J Gastroenterol. 2021; 116: 1336-1338Crossref PubMed Scopus (2) Google Scholar, 53Ketchem C.J. Reed C.C. Stefanadis Z. et al.Treatment with compounded fluticasone suspension improves the clinical, endoscopic, and histologic features of eosinophilic esophagitis.Dis Esophagus. 2021; 34: doaa120Crossref PubMed Scopus (7) Google Scholar, 54Reed C.C. Fan C. Koutlas N. et al.Compounded oral viscous budesonide is effective and provides a durable response in eosinophilic esophagitis.HSOA J Gastroenterol Hepatol Res. 2018; 7: 2509-2515Crossref PubMed Google Scholar Cost simulations show that 6-food elimination diet (SFED) is less expensive and more cost-effective than topical budesonide and fluticasone.55Cotton C.C. Erim D. Eluri S. et al.Cost utility analysis of topical steroids compared with dietary elimination for treatment of eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2017; 15: 841-849Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Although the recent Food and Drug Administration–approval of dupilumab heralds an era of new treatment possibility for EoE, it remains to be seen if insurance coverage for this high-cost biologic therapy will allow patients long-term maintenance care. The overarching goal of dietary therapy is to maintain disease remission by avoiding specific foods that trigger the T helper cell type 2 response in the esophageal epithelium. This process to identify food triggers includes the following phases: (1) the elimination phase, which involves removing a set of foods to first induce disease remission (defined by at least 6 biopsies with significant improvement in eosinophilia, ideally <15 eos/hpf, symptom improvement, improved endoscopic findings); (2) the reintroduction phase, which involves systematically reintroducing food allergen groups in order to isolate EoE food triggers that precipitate active disease; and (3) the maintenance phase, which involves long-term avoidance of the identified food triggers (Figure 1). As this process involves strict avoidance of 1 or more foods, then careful reintroduction of excluded food allergen groups, adequate patient education, and partnering with a dietitian is essential to increase success in all phases of the diet and long-term adherence. Because symptoms are often discordant with underlying disease activity, symptoms alone should not be used to make decisions about treatment changes.56Safroneeva E. Straumann A. Coslovsky M. et al.Symptoms have modest accuracy in detecting endoscopic and histologic remission in adults with eosinophilic esophagitis.Gastroenterology. 2016; 150: 581-590.e4Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar Relying on symptoms in isolation to guide food elimination or reintroduction is insufficient and can result in false identification of food triggers and unnecessarily prolonged dietary restriction. Patients should be warned that their trigger foods are not necessarily the foods that cause immediate symptoms related to obstruction (eg, commonly meats, bread, sticky textures). Endoscopy with biopsy is the gold standard for monitoring response to therapy and is recommended at least 6–8 weeks after a change in therapy, including elimination and reintroduction phases to identify of food triggers.57Aceves S.S. Alexander J.A. Baron T.H. et al.Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference.Gastrointest Endosc. 2022; 96: 576-592.e1Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Tracking progress through each phase of the diet and responses to each food can be helpful, particularly in the case of several identified food triggers or more restrictive diets (Supplementary Material). Initial standard empiric diet strategies include the SFED, 4-food elimination diet (4FED), 2-food elimination diet (2FED), and 1-food elimination diet (1FED). The most well studied and prototypic of these is the SFED—avoidance of all animal milk products, wheat, soy, eggs, nuts/tree nuts, and seafood (finfish and shellfish)—yielding pooled response rates of ∼70% in both children and adults.5Kagalwalla A.F. Sentongo T.A. Ritz S. et al.Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2006; 4: 1097-1102Abstract Full Text Full Text PDF PubMed Scopus (601) Google Scholar,7Gonsalves N. Yang G.Y. Doerfler B. et al.Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors.Gastroenterology. 2012; 142: 1451-1459Abstract Full Text Full Text PDF PubMed Scopus (504) Google Scholar,9Lucendo A.J. Arias A. Gonzalez-Cervera J. et al.Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease.J Allergy Clin Immunol. 2013; 131: 797-804Abstract Full Text Full Text PDF PubMed Scopus (321) Google Scholar Targeting the more common EoE trigger foods, the less restrictive options of the 4FED (avoidance of animal milk, wheat, soy, eggs), 2FED (animal milk and wheat), or 1FED (animal milk only) offer less food avoidance, abbreviated reintroduction phases, and fewer endoscopies to identify potential triggers.10Gonsalves N. Doerfler B. Schwartz S. et al.Prospective trial of four food elimination diet demonstrates comparable effectiveness in the treatment of adult and pediatric eosinophilic esophagitis.Gastroenterology. 2013; 144S-154Abstract Full Text PDF Google Scholar,12Molina-Infante J. Arias A. Barrio J. et al.Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study.J Allergy Clin Immunol. 2014; 134: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar,14Kagalwalla A.F. Wechsler J.B. Amsden K. et al.Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2017; 15: 1698-1707Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar,15Wechsler J.B. Schwartz S. Ross J.N. et al.Cow's milk elimination for treatment of eosinophilic esophagitis: a prospective pediatric study.Gastroenterology. 2017; 152S-855Abstract Full Text PDF Google Scholar However, the trade-off is lower response rates (Table 1). In contrast to the traditional top-down elimination approaches, a step-up strategy beginning with less restrictive diets (1FED or 2FED) and further restricting the diet to the 4FED or SFED if there is nonresponse allows patients to avoid the most common triggers first and potentially fewer number of endoscopies to identify the triggers (Figure 2).58Molina-Infante J. Arias A. Alcedo J. et al.Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study.J Allergy Clin Immunol. 2018; 141: 1365-1372Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar The most identified food triggers for EoE are animal milk (up to 90%) and wheat (up to 75%), and up to half of patients who undergo dietary therapy will have more than 1 dietary trigger.58Molina-Infante J. Arias A. Alcedo J. et al.Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study.J Allergy Clin Immunol. 2018; 141: 1365-1372Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar,62Zhan T. Ali A. Choi J.G. et al.Model to Determine the optimal dietary elimination strategy for treatment of eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2018; 16: 1730-1737Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In a recent study of adult patients undergoing dietary therapy with the SFED, 69% of patients had only 1 food trigger identified, making this a reasonable option for long-term therapy.59Zalewski A. Doerfler B. Krause A. et al.Long-term outcomes of the six-food elimination diet and food reintroduction in a large cohort of adults with eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 1963-1970Crossref PubMed Scopus (5) Google ScholarTable 1Summary of Empiric Elimination Diet StrategiesDietEliminated FoodsaCaveat of systematic reintroduction of foods to identify specific triggers to follow.Pooled Response Rates (%)11Arias A. Gonzalez-Cervera J. Tenias J.M. et al.Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis.Gastroenterology. 2014; 146: 1639-1648Abstract Full Text Full Text PDF PubMed Scopus (386) Google Scholar,12Molina-Infante J. Arias A. Barrio J. et al.Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study.J Allergy Clin Immunol. 2014; 134: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar,14Kagalwalla A.F. Wechsler J.B. Amsden K. et al.Efficacy of a 4-food elimination diet for children with eosinophilic esophagitis.Clin Gastroenterol Hepatol. 2017; 15: 1698-1707Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar, 15Wechsler J.B. Schwartz S. Ross J.N. et al.Cow's milk elimination for treatment of eosinophilic esophagitis: a prospective pediatric study.Gastroenterology. 2017; 152S-855Abstract Full Text PDF Google Scholar, 16Mayerhofer C. Kavallar A.M. Aldrian D. et al.Efficacy of elimination diets in eosinophilic esophagitis: a systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2023; (Jan 31 [E-pub ahead of print])Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar,58Molina-Infante J. Arias A. Alcedo J. et al.Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study.J Allergy Clin Immunol. 2018; 141: 1365-1372Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar, 59Zalewski A. Doerfler B. Krause A. et al.Long-term outcomes of the six-food elimination diet and food reintroduction in a large cohort of adults with eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 1963-1970Crossref PubMed Scopus (5) Google Scholar, 60Kliewer K. Aceves S. Atkins D. et al.Efficacy of 1-food and 4-food elimination diets for pediatric eosinophilic esophagitis in a randomized multi-site study.Gastroenterology. 2019; 156:S-172–S-173Abstract Full Text PDF Google Scholar, 61Kliewer K.L. Gonsalves N.D. Dellon E.S. et al.One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial.Lancet Gastroenterol Hepatol. 2023; (Feb 27 [E-pub ahead of print])Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarProsCons6-food eliminationAnimal milkWheatEggSoyNuts/tree nutsFish/shellfish40–73-Most well studied of the empiric elimination diets-Highest histologic remission rate for empiric elimination diets-Most restrictive of the empiric elimination diets-High number of endoscopies-Cost-Adherence4-food eliminationAnimal milkWheatEggSoy41–60-Less restrictive-Greater diet variety-Shortened diagnostic process-Possible lower remission rate-Cost-Adherence2-food eliminationAnimal milkWheat43bData from Molina-Infante et al.58-Even less restrictive-Avoids unnecessary restriction-Shortened diagnostic process-Impact on quality of lifecQuality of life may be patient dependent.-Possible lower remission rate-Impact on quality of lifecQuality of life may be patient dependent.1-food eliminationAnimal milk34–65-Least restrictive diet-Avoids unnecessary restrictions-Shortened diagnostic process-Less endoscopies-Impact on quality of lifecQuality of life may be patient dependent.-Possible lower remission rate-Impact on quality of lifecQuality of life may be patient dependent.a Caveat of systematic reintroduction of foods to identify specific triggers to follow.b Data from Molina-Infante et al.58Molina-Infante J. Arias A. Alcedo J. et al.Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: the 2-4-6 study.J Allergy Clin Immunol. 2018; 141: 1365-1372Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholarc Quality of life may be patient dependent. Open table in a new tab To date, there are no clinical guidelines or recommendations supporting 1 ideal dietary approach for EoE. Key considerations in diet selection are patient preferences and lifestyle, and provider resources to support varying levels of dietary challenges. More restrictive diets in which multiple common food groups are avoided (eg, SFED) not only are more challenging for patients, but also require providers to be familiar with how to restrict, reintroduce specific foods without contamination, and monitor responses to each phase of the diet. Guided by available evidence-based knowledge, providers ought to weigh the advantages and disadvantages of various dietary strategies with patients (Table 1). Many patient-level factors must be assessed when considering candidates for EoE dietary therapy, such as patient motivation, preferences and values, age or stage of life, lifestyle, work and living situation, willingness for frequent endoscopies, and possibly finances and insurance coverage for several endoscopies and dietitian costs (Table 2). Screening for cost or adherence barriers to implementing the diet, taking an inventory of the patient's diet history, and assessment of current nutritional status are important in this decision.63Chehade M. Brown S. Elimination diets for eosinophilic esophagitis: making the best choice.Expert Rev Clin Immunol. 2020; 16: 679-687Crossref PubMed Scopus (12) Google Scholar In addition to offering diet as an effective and viable alternative to medication, one must work with the patient to weigh these factors in choosing a therapy plan that is concordant with patient preferences and successful. Although not addressed in detail here, particular care and involvement with a dietitian is necessary for pediatric patients on dietary therapy given specific considerations for growth, development, feeding ability and screening for feeding aversion disorders, and parent and family preferences.Table 2Considerations in Patient SelectionConsidering a Patient for EoE Dietary Therapy•High patient desire and motivation to undergo dietary therapy and/or avoid medications•Patient personal preferences and values•Patient's age, life stage, living situation, lifestyle (including travel, dining-out habits) to enable ability to shop for and adhere to a strict diet•Patient's nutritional status and any self-restrictive behaviors toward foods•Patient's willingness to have and travel for frequent endoscopies•Patient's finances and insurance coverage (if high deductibles for procedures)EoE, eosinophilic esophagitis. Open table in a new tab Table 3Checklist for a Dietary Approach to EoEProviders should perform an initial office visit to understand the patient's symptoms, current diet, past experiences with treatments, concerns, values, and preferences for disease management.Given the various dietary strategies and elimination options, providers should individualize the elimination diet to meet the patients' needs.If available, providers should identify a dietitian or nutritionist to partner with.Potential barriers to diet adherence should be explored before starting the diet (eg, high deductible for endoscopies, inability to prepare meals).All patients should be counseled about time commitment and number of endoscopies to anticipate during dietary therapy, with the ultimate goal of identifying trigger vs safe foods.All patients on dietary therapy should have endoscopy with biopsies to monitor responses to the elimination and individual food reintroduction phases.Current restrictive dieting behaviors or previous history of eating disorder should be considered carefully before embarking on diet elimination. In patients already on prolonged and overly restrictive diets, the benefit of dietary therapy should be weighed against the risk of malnutrition. A history of eating disorder does not prevent using dietary therapy but may influence the level of dietary restriction considered for treatment.EoE, eosinophilic esophagitis. Open table in a new tab EoE, eosinophilic esophagitis. EoE, eosinophilic esophagitis. As a hallmark of EoE dietary therapy, an empiric elimination approach involves dietary avoidance of 1 or more common food allergens without prior allergy-based testing.64Kliewer K.L. Cassin A.M. Venter C. Dietary therapy for eosinophilic esophagitis: elimination and reintroduction.Clin Rev Allergy Immunol. 2018; 55: 70-87Crossref PubMed Scopus (17) Google Scholar After selection of the planned diet, patients should be educated on how to avoid specific food allergens (Supplementary Material). These skills include nutrition label reading to avoid contamination, cross-contact, and accidental ingestion. Because the threshold level of an EoE food trigger is unknown, a strict avoidance of the food allergen group and all sources of cross-contamination is recommended during the initial phases of diet to clearly identify the specific EoE triggers. A wheat-free diet should also exclude gluten-containing grains (eg, oats, barley, rye) due to risk of cross-contamination.65Kliewer K.L. Venter C. Cassin A.M. et al.Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?.J Allergy Clin Immunol. 2016; 137: 1011-1014Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Practical tips such as navigating the supermarket, sharing sample menus, and ingredient substitutions can optimize patients' experience and adherence during this more restrictive phase (Supplementary Material).66Doerfler B. Bryce P. Hirano I. et al.Practical approach to implementing dietary therapy in adults with eosinophilic esophagitis: the Chicago experience.Dis Esophagus. 2015; 28: 42-58Crossref PubMed Scopus (52) Google Scholar As the process of an EoE food trigger causing active disease is not immediate, patients are recommended to remain on the elimination phase for at least 6–8 weeks before endoscopy is performed to assess the response to therapy. Once disease remission is attained in a patient eliminating more than 1 food, reintroduction of foods can begin under physician guidance to identify specific trigger foods. Providers should be aware that some patients may require prolonged elimination to achieve disease remission and benefit from an extended course of dietary elimination (at least 12 weeks) if incomplete response (ie, not yet full response but decreased eosinophilia, improved symptoms, and endoscopic findings) is observed or dietary contamination is suspected after the initial 6- to 8-week assessment.59Zalewski A. Doerfler B. Krause A. et al.Long-term outcomes of the six-food elimination diet and food reintroduction in a large cohort of adults with eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 1963-1970Crossref PubMed Scopus (5) Google Scholar,67Philpott H. Dellon E. Histologic improvement after 6 weeks of dietary elimination for eosinophilic esophagitis may be insufficient to determine efficacy.Asia Pac Allergy. 2018; 8e20Crossref PubMed Google Scholar The most common reasons for nonresponse to the elimination phase include purposeful or inadvertent dietary nonadherence, cross-contamination, and incorrect or inadequate removal of potential food triggers. If individuals are unable to attain remission with the initial elimination, taking a detailed history to assess if contamination or adherence should be the first step. There are also data to suggest that the presence of aeroallergen disease may attenuate the response to therapy.68Pesek R.D. Rettiganti M. O'Brien E. et al.Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis.Ann Allergy Asthma Immunol. 2017; 119: 177-183Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 69Ram G. Lee J. Ott M. et al.Seasonal exacerbation of esophageal eosinophilia in children with eosinophilic esophagitis and allergic rhinitis.Ann Allergy Asthma Immunol. 2015; 115: 224-228.e1Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 70Reed C.C. Iglesia E.G.A. Commins S.P. et al.Seasonal exacerbation of eosinophilic esophagitis histologic activity in adults and children implicates role of aeroallergens.Ann Allergy Asthma Immunol. 2019; 122: 296-301Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar As a result, working with an allergist to evaluate the potential role of aeroallergens, seasonality, and environmental allergens can be helpful. If no contamination or nonadherence are identified, patients should be presented with an opportunity to remove further food triggers if they started on a less restrictive diet (eg, further restrict to the SFED if started on the 4FED, or restrict to the 4FED from the 2FED) or prolong the elimination phase for an additional 6–8 weeks before again assessing response. In in a recent study of adults undergoing the SFED, 27% had increased response with a repeated attempt at diet elimination, highlighting this option for motivated patients.59Zalewski A. Doerfler B. Krause A. et al.Long-term outcomes of the six-food elimination diet and food reintroduction in a large cohort of adults with eosinophilic esophagitis.Am J Gastroenterol. 2022; 117: 1963-1970Crossref PubMed Scopus (5) Google Scholar This and any decisions to engage in restrictive diets beyond the SFED (ie, to include corn, legumes, or beef) ought to involve continued careful shared decision making between the patient and clinician, and dietitian if available.